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: INTRODUCTION
Fluconazole is a triazole antifungal agent with its pharmacokinetic properties can be administered orally, parentral and have a good absorptions and not affected by food having Plasma Half-life of 30 hrs where 80% of the dose is excreted out by urine elimination rate is dependent to dose and Fluconazole plasma concentration over the dose range. No effect can be seen on Estrogen, Testosterons, Progesterones, Steroid hormones ( Devaranjan PV Int j Pharm.2012) and no interaction between oral contraceptive. Patient who is receiving anticoagulant should be warned because there is an interaction between Fluconazole if not monitored then can get transplant recipients in the treatment of these infections with taking the dosing range between (50mg-400mg) in a day of Fluconazolebu the side effect took place should be reported (9.3%) and only (91.1%)of all patients were withdrawn from this therapy toxicity, (Bendayan R, j pharmacol Exp Ther, 2006) is observed (9%) with the patient treated with Fluconazole and whereas (67%) in Amphotericin B and having less Nephrotoxity than Amphotericin B polimer lipid hybrid nanoparticles (PHLN) are composed of Liposomes and nanoparticles into a single delivery system having a two functional components which are:
• Hydrophilic or Hydrophobic polymer here the drug soluble with high yields.
• Highly compatible shell having surrounding a lipid layer core and the molecular force provided for the promote of drug retention inside polymeric core which is having a compatibe shell.
In the case of transmission of bacterial, viral, fungal infection disease increases year by year in the form of transmission from person to person and recently years became more common (500%) growth in blood stream infections with Candida since 1980 ( Jain AK j.biomaterials.2010) The azole anti fungal agent represents various maximum used drug classes for the treatment of infections these are: Triazole and Imidazole.
Transcellular pathway crosses the epithelial cell barrier it included transcellular like:
• Transport of cell
• Transcytosis
• Crossing of cell membrane.
M.cells are the mechanism to transport te nanoparticles across intestinal barrier. M cell contains Peyer’s Patches (PP), Gur associated Lymphoid tissue (GALT) M cell reduce mucus secretions, Glycocalyx, protease. ). (ZhaoX J control release.2008) Solid lipid nanoparticles, polymeric nanoparticles, nanoemulsion nanoparticles are capable of enhancing absorption which is poorly soluble drug. Polymer lipid hybrid nanoparticles having the advantage of Liposome and Polymeric nanoparticles because they excluded intrinsic limitations and can posses the delivery vehicles for various drugs.
1 TYPES OF NANOPARTICLES:
• Solid lipid Nanoparticles
• Functionalized Nanocarriers
• Nanocapsule
• Ceramic Nanoparticles
• Hydrogel Nanoparticles ( Rauth AM j pharmacol Exp Ther 2006)
• Nanospheres
• Polymeric Nanoparticles
• Nanotubes and Nanowires
1.2 ADVANTAGE OF NANOPARTICLES:
• Administered parentrally, orally, nasal.
• Improves toxic effect, therapeutic index, stability( Kim J-K Int J Pharma.2008)
• Active and passive drug targeting can be achieved.
• Used for directing the drugs to target the cells.
1.3 DISADVANTAGE OF NANOPARTICLES:
• Limited drug loading.
• Toxic metabolites can occur
• Physical handling can be difficult in liquid and dry stage.
• Administered parentrally, orally, nasal.
1.4 METHODS OF PREPARATION OF NANOPARTICLES:
• Polymerization.[Pandurangan P, Ramasami N]
Dispersion polymerization (DP).
Emulsion polymerization (EP).
• Preformed polymerization (PP). (Benival DM j.injpharm.2011).
Solvent evaporation.
Solvent displacement.
Salting out technology.
• Super critical fluid technology.
CHAPTER 2: OBJECTIVES OF THE STUDY
Aim of present studies to prepare and evaluate polymer lipid hybrid nanoparticles of Fluconazole with an anticipated increase in bioavailability and reduction of dose and thus dose related side effects by using various and effective nanomethods
3.1 REVIEW OF PAST WORK DONE ON POLYMERIC LIPID HYBEID NANOPARTICLES:
Rohit R. Bhosale (2015)
He was carried his research work on solid lipid hybrid nanoparticles (SLHN) for he drug delivery system with having various applications in pharma and cosmetics research plus nanomedicines also been observed that solid lipid hybrid nanoparticles in corporating with Lipophillic, Hydrophillic drug protein and antigen to in corporated into it. It also administered parentally, orally, nasal all the special properties of solid lipid nanoparticles and carries nano carrier into it and the problem of cancer chemotherapy can also be overcome by Solid lipid nanoparticles.
Desai AS (2014)
He was carried his research work on nail lacquer which contains fluconazole for transsungal drug delivery system using ethyl cellulose it is polymer fluconazole act by 14-α demethylase which is a cytochromeP450 enzyme which later converts into lanosterol to ergosterol and it inhibits the permeability of cellular membrane of fungi and causes leakage of cellular membrane and its components. He was prepared the formulationtions which was evaluated in different parameters like smoothness, Drying timing, glossing, resistance, drug content, In- vitro studies, Kinetic studies. By using 35 optimized formulations for further studies and then product was studied to different parameters like fungal testing, stability testing, kinetic studies.
Gupta M (2013)
He was carried his research work on dermal delivery of fluconazole this is done due to the problem relating to its therapeutic efficiency and drug release control the main subject is fluconazole nanopaticles which carried lipid core to optimized the drug retention into the skin. Solid lipid hybrid nanoparticles were formed by In-vitro, solvent diffusion method, drug content, entrapment efficiency (4.94%) and particle size (3.8%), In –vivo data shows drug release over 24hrs lipid (CA) is taken for improvement in dermal found SLNs with CA lipid is a good carrier for the treatment on topical bases of skin infections for systemic circulations.
Bhargav R (2012)
He was carried his research work on poly(lactic-co-glycolide) nanoparticles with Azithromycin which is having anti-microbiological activity and physicochemical properties prepared by taking three ratios of drug and polymer nano - precipitation technique here the anti bacterial activities of nanoparticles were using against (Salmonella thyi) absorbance was taken (222nm to 262nm) by using nanoscale size particles and entrapment efficiency was (4.3%) under drug and polymer ratios, zeta potential was 1:4 and totally negative, X-Ray detected the amorphous state, FTIR spectroscopy shows there was no interaction between drug and polymer, In- vitro shows two phases 4hr which is a slow release pattern within 24hrs all parameters shows that the nanoparticles are more effective than Azithromycin and concentration was (1/9) of drug an can be used for oral administration.
Devi S (2011)
He was carried his research work on silver nanoparticles here shows that it having an good attention and getting more focused on research due to its high chemical, stable and thermal properties and it is environmental friendly and low cost techniques are applied to it. In this research the silver nanoparticles were synthesized by using aqueous Gracilaria drug(AG) as the reducing agent. The visibility of the silver nanoparicles confirmed by its colour changing properties like using UV spectroscopy, FTIR shows the presence of protein, X-Ray diffraction methods detected the elemental silver, the absorbance was (445nm),results shows the Green colour for nanoparticles.
Parimi U (2010)
He was carried his research work on green synthesized silver nanoparticles due to there catalysis, chemistry medicine, electronic uses in the pharmaceutical fields here it is not environmental and made a report on rapid and satisfied silver nanoparticles using silver nitrate all the components are used in the parameters like UV spectroscopy, FTIR, In-Vitro, entrapment efficiency. Green silver nanoparticles showed the anti fungal, anti bacterial activities against Gram- Negative bacteria (Bacillus Subtilis) and Gram- Negative bacteria (Salmonella typi) and anti fungal like (Candida albicans) the nanoparticles were found to be very toxic against fungal infections